Method of thermal treatment for myolysis and destruction of benign uterine tumors

ABSTRACT

A high-power ultrasound heating applicator for minimally-invasive thermal treatment of uterine fibroids or myomas. High-Intensity interstitial ultrasound, applied with minimally-invasive laparoscopic or hysteroscopic procedures, is used to effectively treat fibroids within the myometrium in lieu of major surgery. The applicators are configured with high-power capabilities and thermal penetration to treat large volumes of fibroid tissue (&gt;70 cm 3 ) in short treatment times (3-20 minutes), while maintaining three-dimensional control of energy delivery to thermally destroy the target volume.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/738,391 filed on Apr. 20, 2007, now U.S. Pat. No. ______,incorporated herein by reference in its entirety, which claims thebenefit of U.S. provisional patent application Ser. No. 60/885,845 filedon Jan. 19, 2007, incorporated herein by reference in its entirety, U.S.provisional patent application Ser. No. 60/797,421 filed on May 3, 2006,incorporated herein by reference in its entirety, and U.S. provisionalpatent application Ser. No. 60/793,750 filed on Apr. 20, 2006,incorporated herein by reference in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

INCORPORATION-BY-REFERENCE OF COMPUTER PROGRAM APPENDIX

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NOTICE OF MATERIAL SUBJECT TO COPYRIGHT PROTECTION

A portion of the material in this patent document is subject tocopyright protection under the copyright laws of the United States andof other countries. The owner of the copyright rights has no objectionto the facsimile reproduction by anyone of the patent document or thepatent disclosure, as it appears in the United States Patent andTrademark Office publicly available file or records, but otherwisereserves all copyright rights whatsoever. The copyright owner does nothereby waive any of its rights to have this patent document maintainedin secrecy, including without limitation its rights pursuant to 37C.F.R. §1.14.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention pertains generally to treatment of uterine fibroids, andmore particularly to ultrasound therapy of uterine fibroids.

2. Description of Related Art

Uterine fibroids, also known as leiomyomas or myomas, are the mostcommon solid pelvic tumor occurring in women, and are the reason fornearly 30% of hysterectomies performed in the U.S. Further, it has beenestimated that 25-50% of women of reproductive age have one or moreuterine fibroids, and the incidence is as much as 9 times higher inblack women than in white women. Depending on the size, number andlocation of the fibroids, symptoms can be severe, and often includeexcessive or persistent menorrhagia, pelvic pain and cramping, pressure,urinary problems, constipation, anemia, or infertility. Another concernis the degeneration of fibroids to malignant leiomyosarcomas, at anincidence rate of approximately 0.5%.

FIGS. 1A and 1B are anatomical sketches contrasting a healthy patient 10having a normal uterus 22 with a second patient 12 having a uterusshowing growth of uterine fibroids in various regions. Fibroids arenodules of well-differentiated smooth muscle encased in fibrous tissuethat grow in or on the wall of the uterus, with some reports of myomasdemonstrating skeletal muscle differentiation. Fibroids range in sizefrom approximately 0.5 cm to greater than 10 cm in diameter, and maygrow as submucosal fibroids 30 just beneath the endometrium 14(submucous), as intramural fibroids 36 within the myometrium 16(intramural), or subserosal fibroids 28 beneath the serosa. They mayalso be pedunculated, and reside either within the uterine cavity 22(pedunculated submucosal fibroids 34), or outside the uterus 22 in thepelvic cavity (pedunculated subserosal fibroids 32).

Treatment options for women considering bearing children are limited.The most common and permanent treatment for uterine fibroids is surgicalremoval of the uterus (hysterectomy), particularly in women approachingmenopause. Although a permanent solution for fibroids, hysterectomy is amajor surgical procedure associated with significant risk ofmortality/morbidity including fever, wound infection, excessive bloodloss, increased risk for transfusion, and trauma to the bladder andsurrounding tissues. Recent improvements in hysterectomies performedusing a vaginal approach have demonstrated reductions in blood loss,post-op complications, length of hospital stay, and overall cost.However, vaginal hysterectomies are not recommended for patientspresenting with a large fibroid uterus.

For pre-menopausal women wishing to retain their uterus forreproductive, psychological or hormonal reasons, myomectomy (surgicalremoval of fibroids) can be a less invasive alternative to hysterectomy.The procedure may be performed via open laparotomy, or via a number ofadvanced laparoscopic and hysteroscopic surgical techniques. For womenconsidering childbearing, preferred surgery is the open myomectomy inorder to preserve the structural integrity of the uterine wall—theability to apply multiple layers of suturing is severely limited forlaparoscopic procedures. While complications are similar to those ofhysterectomy, the complication rate is reduced from 25% to as low as14.8%, and fertility may be improved, with pregnancy rates reported ashigh as 74%. However, the incidence of post-operative adhesions may beas high as 89%, and the risk of recurring fibroids requiring additionalsurgery or hysterectomy is 15-25%.

Hormonal therapies such as gonadotrophin releasing hormone (GnRH)agonists can be used to induce artificial menopause resulting in a30-40% decrease in fibroid size, and a 40-50% reduction in uterinevolume. The side effects experienced with hormonal therapies are similarto symptoms often associated with menopause (hot flashes, irregularvaginal bleeding, vaginal dryness, headaches, and depression). However,prolonged use may result in excessive bone loss, and the fibroids willreturn to their pre-treatment volumes within 3 months if treatment isdiscontinued. Rather than a long term treatment option, hormonaltherapies are often used prior to myomectomy to reduce the size of theuterus and the fibroids thus facilitating the surgical procedure.

Uterine artery embolization (UAE) is a minimally-invasive surgicalprocedure used to treat fibroids by obstructing their blood supply. Acatheter, advanced into the uterine artery under fluoroscopic guidance,is used to inject polyvinyl alcohol particles resulting in immediateobstruction of blood flow. Clinical studies indicate that UAE reducesfibroid volume by approximately 35-60%, and has been effective in 85% ofthe patients. Complications of the procedure include risk of allergicreaction to medications, infection, contrast-induced renal failure,uterine perforation, sexual dysfunction, and post-procedure painattributed to the ischemic necrosis. Fibroid sloughing requiringadditional surgery occurs in about 10% of the patients.

Laparoscopic myoma coagulation (myolysis) is a minimally-invasiveprocedure in which a laser or a radiofrequency (RF) needle is used tothermally coagulate and necrose uterine fibroids and their vascularsupply. Both modalities can be used to thermally coagulate and reducethe size of uterine fibroids by as much as 40 to 50%. However, a recentclinical study using an RF needle electrode with extendible secondaryelectrodes to treat large fibroids demonstrated the ability to produce a5 cm diameter region of necrosis resulting in as much a 77% reduction infibroid volume. Yet spatial control of the pattern is very difficult, ifnot impossible. An advantage of myolysis performed using a laser fiberis that treatment can be guided and monitored in real time with MRthermal monitoring techniques. However, since the propagation of energy,and hence coagulation of tissue, is limited to a radial distance of lessthan 1 cm from the applicator at a single puncture, high power levels,multiple punctures (sometimes >50) and longer treatment times are oftenrequired to treat commonly occurring large myomas (5+ cm diameter) usingeither RF or laser modality. Techniques using either sequentialinsertions or multiple, simultaneously implanted laser fibers around thecircumference of the fibroid have been used to coagulate the outerboundary, thus destroying the blood supply and shrinking the fibroid.Although major complications with this technique are rare, the risk ofpost-operative adhesions increases with the greater number of deviceinsertions required to heat larger fibroids. Control of thermalcoagulation with these technologies is determined by applied power only,with no dynamic angular or longitudinal spatial control of heating alongthe length of the applicator, or radially/angularly from it.

The feasibility of using cryotherapy for treatment of fibroids has beeninvestigated. Initial studies demonstrated an overall reduction infibroid size of only 10%; recent studies have shown clinical resultssimilar to those obtained by other minimally-invasive treatments withmean volume reductions up to 65%. Furthermore, this technology can beused with interventional MR imaging for visualization and guidance ofthe cryoneedles, and monitoring of the freezing procedure. Control ofthe freezing zone is problematic. Complications of this technique aresimilar to those associated with thermal coagulation methods. Theapplicator diameters range 3-5 mm, and are introduced with trocars andintroducer sheaths similar to our proposed procedure.

In some, the above thermal techniques (e.g. cryotherapy orhigh-temperature thermal ablation) have at least one of the followinglimitations: inability to spatially control the distribution of energyoutput to conform to the fibroid volume, inadequate single treatmentvolumes requiring multiple device insertions (increases risk ofadhesions), long procedural times, or limited use due to proximity ofcritical tissue structures (e.g., bladder, bowel). These limitations mayreduce their effectiveness and overall applicability to consistently andsafely treat symptomatic fibroids.

High-intensity externally-focused ultrasound (HIFU) is a another,non-invasive method used to generate well-localized thermal damage deepwithin the body, while possibly avoiding damage to the overlaying orsurrounding tissues. Although this technique is non-invasive and capableof precise coagulation of tissue, long treatment times (>2 hours) arerequired to treat small tissue volumes (12 cm³), access to fibroidslocated in proximity to bowel or bladder is limited, and lack ofadequate acoustic window and pre-focal heating limits this technology toaccessible small fibroids. Significant reported complications includethermal damage or burns in deep tissue, bowel, and superficial tissuelayers, including the skin beneath the acoustic interface.

There is a substantial clinical need for a minimally-invasivealternative to traditional open surgical approaches with the promise ofless morbidity and recovery time, faster procedure time, and lower cost.Interstitial ultrasound has potential to provide a superiorminimally-invasive heating technique for the laparoscopic treatment ofuterine fibroids with the promise of more precise and thoroughtargeting, accessibility to a larger number of fibroids, fasterprocedure times, and repeatable performance acceptable to thegynecological surgeon.

BRIEF SUMMARY OF THE INVENTION

The present invention may be used to treat fibroids, including onesconsidered too large for existing heating technologies, by usingultrasound energy to heat or ablate the fibroid or a portion of thefibroid. The ultrasound system and methods of the present inventionallow directional control and deep penetration of energy patterns fordirected thermal arterial occlusion/coagulation. With the system of thepresent invention, large fibroids can be treated by targeting a smallerportion of the tumor with the feeding vasculature, thus reducing thetreatment time and improving chances for complete regression. Inaddition, this requires less of a volume be thermally fixed ordestroyed, which may remain in the body for some time and in somecircles considered clinically undesirable.

The present invention is directed to a high-power intracavitary andinterstitial ultrasound heating applicators for minimally-invasivethermal ablation of uterine fibroids or myomas. High-Intensityintracavitary and interstitial ultrasound, applied withminimally-invasive laparoscopic or hysteroscopic procedures, is used toeffectively treat fibroids within the myometrium in lieu of majorsurgery, providing a better alternative treatment for women wishing tobear children. The applicators of the present invention are configuredwith high-power capabilities and thermal penetration to treat largevolumes of fibroid tissue (>70 cm³) in short treatment times (3-20minutes), while maintaining three-dimensional control of energy deliveryto thermally destroy the target volume. Directional or selective heatingmay be used as a means of preserving surrounding healthy tissue, forexample to avoid bladder, bowel or other sensitive organs.

An aspect of the invention is an apparatus for treating uterinefibroids, having a catheter with a distal end and a proximal end and anultrasound applicator disposed at the distal end of the catheter. Theapplicator has one or more transducers disposed longitudinally along acentral axis of the catheter, wherein the one or more transducers arecoupled to a power source external to the catheter. In particular, theultrasound applicator is configured to be positioned to a treatmentlocation at or near a fibroid tissue mass and deliver high-intensityultrasound energy sufficient to heat and destroy the fibroid tissuemass. The delivered energy is sufficient to ablate or necrose thefibroid tissue.

In a preferred embodiment, the applicator is configured such thatsufficient energy is applied to treat the fibroid tissue within a periodranging between approximately 3 to 20 minutes, and preferably 5 to 15minutes.

The applicator ideally comprises an array of two to five transducers,and more preferably three to four transducers. In one embodiment, thetransducers are tubular and disposed adjacent each other over a supportelement in a linear array.

In another embodiment, the transducers are configured to providedirectional energy distribution of the ultrasound energy in a firstdirection associated with the fibroid while shielding ultrasound energyin a second direction. The transducers may be configured to emitultrasound energy in a substantially 360° pattern radially from the axisof the catheter, or emit a radial pattern less than 360°, e.g. 180°,120°, or 90°, etc. In addition, the transducers may be sectored andindividually wired to each emit a portion of a 360° radial pattern.Additionally, the transducers may be each arcuate and emit focusedenergy as a line focus in a specific direction pointing into thefibroid, which may be selected by rotating the transducer.

The ultrasound transducers may be disposed within the catheter, (e.g.emit through the catheter walls, or be disposed adjacent to the distalend of the catheter.

The catheter may also be configured to provide fluid cooling to theultrasound elements. In one embodiment, the applicator further comprisesa balloon emanating at the distal end of the catheter, wherein theballoon configured to surround the one or more transducers to circulatethe cooling fluid around the one or more transducers. The catheter mayalso comprise a multi-lumen catheter with a first lumen configured todeliver fluid to the applicator, and a second lumen configured totransport fluid out of the applicator.

The device may also comprise a retractable sheath configured to surroundthe applicator during delivery to the treatment site.

In another embodiment, the device includes a temperature probe disposedat the distal end of the catheter, wherein the temperature probe isconfigured to acquire temperature readings at one or more locations oftissue in vicinity to the applicator.

In yet another embodiment, the catheter comprises a bendable portionproximal to the applicator such that the applicator may be oriented atan angle with respect to the catheter proximal to the bendable portion,wherein the bendable portion comprises a material configured to retainthe angle as the applicator is delivered to the treatment site.

The applicator may be configured to be delivered via laparoscopicaccess, hysteroscopic access, or both.

Another aspect of the invention is a method of treating a uterinefibroid. The method includes the steps of positioning an ultrasoundtransducer at a treatment location at or near a fibroid tissue mass, andadministering power to the transducer to deliver high-intensityultrasound energy to the fibroid tissue mass sufficient to heat anddestroy the fibroid tissue mass, e.g. via ablating or necrosing thefibroid tissue.

Prior to delivery of the ultrasound energy, the power, treatment time,and frequency of the ultrasound energy may be determined based on thefibroid tissue anatomy, and input into a computer controlling the energytransmitted from the transducer.

In one embodiment, the ultrasound energy is delivery to only a portionof the fibroid tissue, ideally the portion comprising feedingvasculature.

In another embodiment, a thermal sensor may be deployed to obtaintemperature feedback of tissue at or near the applicator. Also, themethod may include determining the extent of arterial occlusion byapplying one or more of the following diagnostic techniques: such asfluoroscopic, Doppler ultrasound, MRI, or CT imaging.

The energy may be delivered from the applicator in an array oftransducers. In some embodiments, the transducers are individuallyoperable to independently or concurrently deliver ultrasound energy.

In one embodiment, the applicator is delivered to a substantiallycentral location within the fibroid tissue, and is controlled to emitultrasound energy in a substantially 360° pattern radially from an axisof the catheter.

Alternatively, the applicator is delivered to a location substantiallyadjacent the fibroid tissue, and controlled to emit ultrasound energy ina radial pattern less than 360°, e.g. a radial pattern of approximately180° or less.

In another embodiment, the method may include delivering a cooling fluidto the applicator through the catheter during delivery of ultrasoundenergy.

Another aspect of the invention is an apparatus for treating uterinefibroids, having a catheter with a distal end and a proximal end, and anultrasound applicator disposed at the distal end of the catheter. One ormore tubular or arcuate transducers are disposed longitudinally over asupport element that is substantially coincidental with a central axisof the catheter. A power source external to the catheter is coupled tothe one or more transducers. In particular, the ultrasound applicator isconfigured to be positioned at a treatment location to deliverhigh-intensity ultrasound energy sufficient to heat and destroy afibroid tissue mass located at or near the treatment location.

In one embodiment of the current aspect, the applicator comprises anarray of two to five transducers disposed adjacent each other in alongitudinal array, and preferably an array of three to fourtransducers.

Further aspects of the invention will be brought out in the followingportions of the specification, wherein the detailed description is forthe purpose of fully disclosing preferred embodiments of the inventionwithout placing limitations thereon.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

The invention will be more fully understood by reference to thefollowing drawings which are for illustrative purposes only:

FIG. 1A is a diagram of a healthy uterus.

FIG. 1B is a diagram of a uterus with fibroids.

FIG. 2 illustrates a laparoscopic approach to treating fibroids inaccordance with the present invention.

FIG. 3 further illustrates the laparoscopic procedure with theultrasound applicator of the present invention positioned adjacent thetarget fibroid.

FIG. 4 shows a hysteroscopic procedure in accordance with the presentinvention.

FIG. 5 shows a distal tip of a conformable ultrasound applicator of thepresent invention.

FIG. 6 illustrates a liquid-cooled applicator.

FIGS. 7A-7D illustrate side views of various ultrasound elementconfigurations.

FIG. 8 illustrates a flow diagram of an exemplary fibroid treatmentprocess in accordance with the present invention.

FIG. 9 illustrates angular and axial control of power deposition (P²)and heating from in vivo measurements of temperature and zones ofthermal coagulation.

FIG. 10 shows a plot of ultrasound energy distribution of a 200 degreeapplicator.

FIG. 11 is a graph of the treatment depth across the axial position ofthe applicator.

FIG. 12A-12C show a simulation of the radial depth into tissue for one,two, and three element applicators.

FIG. 13 illustrates the 3-D distribution of a 2-transducer applicator.

FIG. 14 illustrates MRI images of the thermal dose delivered to tissueduring application.

FIG. 15 illustrates test results for temperature and thermal dosemeasurements of a 2.4 mm OD ultrasound applicator.

FIG. 16 illustrates an exemplary test set up for testing the ultrasoundapplicator of the present invention on an ex-vivo human fibroid sample.

FIGS. 17-19 illustrate the results of the heating trial in a humanuterine fibroid using a 4-element applicator with 360 degree heatingpattern inserted in a 13 g catheter with 60 ml/min flow rate.

FIG. 20 illustrates a sagittal slice through thermal lesion, visualizedafter 20 minutes in a 2% TTC solution.

FIGS. 21 and 22 illustrate transverse slices through thermal lesions (asvisualized using TTC stain) generated in human uterine fibroids using a3-element applicator with a 180 degree directional heating pattern,inserted in a 3.7 mm OD catheter with 60 ml/min flow rate.

FIG. 23 illustrates untreated tissue showing lighter, heterogeneous andslightly granular chromatin, and visible nuclear features.

FIG. 24 shows treated tissue indicating hyperchromatic nuclei.

FIG. 25 illustrates a three×10 mm transducer applicator and resultingtissue lesion.

FIG. 26 illustrates a four×10 mm transducer applicator and resultingtissue lesion.

FIG. 27 illustrates a lesion created by a two×10 mm transducerapplicator with 180° directional distribution.

FIG. 28 illustrates a lesion created by a 180° directional distributionapplicator and insertion point.

DETAILED DESCRIPTION OF THE INVENTION

Referring more specifically to the drawings, for illustrative purposesthe present invention is embodied in the apparatus and method generallyshown in FIG. 2 through FIG. 28. It will be appreciated that theapparatus may vary as to configuration and as to details of the parts,and that the method may vary as to the specific steps and sequence,without departing from the basic concepts as disclosed herein.

FIG. 2 illustrates the overall schema for laparoscopic interstitialultrasound thermal treatment of a uterine fibroid 30 embedded inmyometrium 16, following procedures similar to those used forlaparoscopic myomectomy or recent RF/cryotherapy ablation studies,providing a simple and minimally-invasive treatment technique.

Multiple access ports 46 (generally three to five) for the laparoscope40 and surgical instrumentation (e.g. catheter 44) may be placed withinthe abdominal wall 48, and the abdominal cavity pressurized with gas.The uterus 22 may be positioned with a standard manipulator 42 and apath to the fibroid 30 cleared.

The ultrasound applicator 50 may be centered or placed eccentric withinfibroid 30 using standard manipulators to position tissues prior toinsertion. Positioning of applicator 50 to the treatment site may beaffected via a working channel of laparoscope 40, or via a dedicatedport as shown in FIG. 2.

Pre-operative imaging studies, direct magnified visualization, and/orthe use of intraoperative ultrasound imaging can be used to determinetreatment parameters a priori and verify device placement, with Dopplerultrasound able to localize feeding vasculature for targeting.

Referring to FIG. 3, the ultrasound therapy device 50 of the presentinvention is configured for insertion directly into the fibroid 30during laparoscopic surgery. The device 50 may comprise a rigidintroducer sheath 62 configured to be inserted into the fibroid 30. Thedevice 50 may also comprise thermometry sensors 66 that deployablewithin the target volume of the fibroid 30. The sheath 62 may beretracted once the high-powered ultrasound applicator 50 is inserted toa predetermined depth.

The applicator 50 of the present invention includes substantial poweroutput (30-50 W/cm² applied power) with controlled heating of largertumor volumes.

High-powered ultrasound may be applied via one or more ultrasoundtransducers 64 positioned at the distal tip of the applicator 50, andmay be applied at preset power levels and duration to conform therapy tothe target zone 70 for the thermal lesion. Applicator transducers 64 maybe at least one of the following: tubular, planar, or arcuate. Theapplicator 50 preferably includes a deployable pre-shaped thermocoupletemperature probe 66 (e.g. nitinol hypodermic tubing, pre-shaped by heatfixation) that is integrated with the introducer sheath 62 and designedto deploy into the target zone 70. Deployable temperature sensing viasensor array 66 provides treatment verification and feedback so thatonly the desired treatment region or target zone is affected.Furthermore, additional protection can be instituted by placing a smallair-gap or acoustic blocking or shielding material 68 between theapplicator and the area to be protected (e.g. bowel 72 or bladder 52).

As shown in FIG. 4, applicator 80 may be configured to deliver treatmenthysteroscopically via vaginal access 24 into uterus 22. Applicator 80may be configured and shaped specifically for this type of procedure, ormay be configured to be used interchangeably for laparoscopy orhysteroscopy.

FIG. 5 illustrates an ultrasound applicator 90 configured to becompliant to bend at a point proximal to distal tip 92 and theapplicator elements 64. In this configuration, the applicator maycomprise a compliant memory material (e.g. nitinol) at location 96 sothat the distal tip 92 may be bent at an angle θ with respect toproximal section 94 as desired by the physician according to the anatomyof the patient and location of the fibroid, and retain its shapethroughout the procedure. In an alternative configuration (not shown),the applicator tip 92 may be steerable by inclusion of one or moreguidewires extending from the proximal end of the catheter to the distaltip. Thus, the applicator tip may be bent to the desired shape while theapplicator is positioned at the treatment location within the patient'sbody by pulling on the guidewire.

The applicator 50, 80, 90 is preferably configured to withstand therigors of laparoscopic surgery, and have support systems and control,manipulators and procedures, specific tooling, treatment feedback andcontrol schemes, and treatment planning schemes based upon pre-operativeand/or intra-operative imaging studies, treatment modeling, on-linereal-time thermal dose monitoring/control.

FIG. 6 illustrates a high intensity catheter-cooled interstitialultrasound applicator 100 of the present invention. A plurality oftransducers 64 are positioned at or near the distal tip 112 of amulti-lumen catheter 102. The number of transducers may vary from 1 toover 5, but preferably range from 2-4 transducers. The transducers aregenerally cylindrical or tubular members that fit sequentially overpolymide support tube 110. Each of the transducers may be separated by acoating 122, which may comprise, for example, a lamination of an epoxy,silicone adhesive and polyester layers or combination of the above.Other layering/materials may be also be used as desired.

Catheter 102 preferably comprises inbound and outbound lumens 106 (e.g.multi-lumen catheter) for cooling water flow 106. The cooling liquid(e.g. water) may be cycled at and around the transducers 64 via inletport 120 and outlet port 118 at proximal end 116 of the catheter. Thecooling liquid may be cycled within a polyester balloon 108 to achieveactive water-cooling of the transducer crystals 64. RF power lines 104may be feed out port 114 for quick-connect leads 124 or like connection.

The applicators 50, 100 may be configured in three primary sizeconfigurations: 1) smaller applicators with a 14-15 g needle/catheter(1.8-2.1 mm OD), 2) larger diameter devices utilizing 8-9 g catheters(3.8-4.2 mm OD) (e.g. placed through a laparoscope 40 working channel),and 3) revision of a 2.4 mm diameter 13 g device to increase powerhandling. The smaller 14-15 g catheters generally represent a lower sizelimit for applicators with the proposed high powers, and can be usedwith existing instrumentation for laparoscopic and hysteroscopicapproaches. Though these smaller sizes are preferred for insertion, thetwo larger devices may be beneficial for attaining maximum powerhandling capability, and can be used with larger trocars and modifiedapproaches for laparoscopic, and hysteroscopic insertion (similar sizesare currently used clinically for cryotherapy probes).

Fabrication of the applicators may be achieved with use of tubularpiezoceramic ultrasound transducers 64 located around polymide tubing100 (see FIG. 6), with an operating frequency of approximately 7 MHz.

For achieving high power output, the tubular ultrasound transducers 64may vary by the type of piezoceramic material, size of the transducercrystal, power handling capability, uniformity of wall thickness,efficiency optimization, electrical impedance, frequency, piezoelectricactivity, electro-acoustic conversion efficiency, consistent poweroutput, and robust coverings. Piezoceramic material selection may bebased on maximum power handling and crystal displacementcharacteristics, using comparisons between PZT-4 and PZT-8.

Transducer 64 diameter may be determined by the size restriction of theexternal catheter, using 1.0-1.5 mm OD tubular transducers for thesmaller 13-15 g catheters, and larger transducers of 3.0-3.5 mm OD tomaximize power output for the larger catheters. Transducer 64 lengthsmay range from approximately 6-20 mm, and be configured to have theappropriate balance between axial power potential and electricalimpedance.

The catheter-cooled ultrasound applicator 100 may utilize Celcon (acetalcopolymer) for the implant catheter 102 material. While this materialhas been sufficient for low to moderate power applications, it may belimited at higher powers due to acoustic properties that partially blockenergy transmission. Suitable catheter materials, e.g. thermoplasticssuch as polycarbonate, polyether (Pebax and Hytrel), nylon 6-6,polyethylene, and polypropylene, may be selected based on a number ofmaterial properties. Criteria used to select the materials may includeboth acoustic properties (acoustic attenuation and impedance) andthermal properties (thermal conductivity, melting temperature, anddeflection temperature), as well as overall stiffness/durability of thematerial and its ability to be extruded, and the optimal combination ofthese material properties to maximize power output. The diameter andthickness of the catheter 102 material are configured for theappropriate applicator dimensions to provide a robust delivery devicewhile minimizing blockage of energy transmission.

The cooling system, mechanisms, and flow schemes of the applicator 50are configured to achieve levels of convective cooling necessary toallow higher levels of applied power (30-50 W/cm² applied power).

The transducers 64 may also be shaped to provide controlled and directedheating of tissue, and maintain control and directionality of tissueheating at higher power levels. Specifically, the shape may beconfigured to maintain longitudinal control (heating control along thelength of the applicator 50) and angular control (heating around theapplicator 50). Multiple transducer elements (for example, but notlimited to 1-5 transducers) may be used to achieve heating lengths of 5cm or greater, as well as to control the length of heating withindividual power to each transducer element with collimated acousticoutput.

The applicators may be fabricated using transducers with 360° angularacoustic output to maximize the potential treatment volume and theuniformity of circumferential heating. In this case, access to thefibroid is such that the applicator 50, 80, 90 may be positioned withina central location in the fibroid, and wherein the fibroid is notdirectly adjacent sensitive organs.

As shown in FIGS. 7A-7C, the applicators may also be fabricated usingtransducers that are sectored to provide a specific angular acousticregion (i.e. 60° to 180°) for placement at the periphery of a targetregion, selectively destroying the tissue on one side while preservingcritical tissue (e.g. bladder, rectum) on the other side. Thisconfiguration is ideal where access to a central location within thefibroid 30 is not available, and to protect anatomy that is adjacent ornear the fibroid 30.

FIG. 7D illustrates an example of an arcuate transducer 156 having aconcave transmission surface 158 configured to produce a focal zoneextending outside of the outer diameter of the catheter 102 into thetissue under treatment. The radius r of the concave surface isconfigured to be larger than the radius of the catheter 102 to ensurethat focus CL (the focused beam path center line for the transduceralong the axis of the catheter) is outside the catheter 102. The radiusr may be varied so that the beam path CL focuses on a desired locationaway from the catheter 102. In this configuration, the applicator may beswept across a path to treat a volume of tissue. For example, theapplicator may be placed adjacent a fibroid 30 outer surface with thesurface 158 and beam path CL pointing inward toward the center of thefibroid. The applicator may then be swept around the fibroid outersurface to treat the entire volume of the fibroid.

As shown in FIG. 7A, element 64 may comprise two notches 130 in thesurface of the element to electrically isolate a first portion (half)132, from a second portion 134. As shown in FIG. 7A, the notches 130 are180° apart from each other, allowing an 180° distribution pattern fromside 132. Only one side may be wired (e.g. section 132) or both may beindividually wired for selective and independent control of each section132, 134.

As shown in FIG. 7B, applicator element 140 may have three or morenotches 130 to have additional sections 140, 142, 144 for individualcontrol. As shown in FIG. 7B, section 142 is configured to emit a 120°distribution beam. Each segment may be operated independently and/orconcurrently, and adjusted according to different levels (e.g. powerfrom 0 to max, frequency, and emission time) for desired coagulation ordistribution.

Referring to FIG. 7C, element 150 may be configured to have electricalcovering 154 etched and removed to have emitting section 154 to have aless than 360° distribution.

The general durability and robustness of the ultrasound applicator 50are a factor of the thermal thresholds and mechanical thresholds forboth transducers 64 and delivery devices.

The applicator 50 of the present invention is optimized for maximumtransducer power output, electro-acoustic efficiency, and acoustic beamintensity distributions. Power may be applied to transducers using a16-channel amplifier system (0-50 W/channel, frequency range 6-10 MHz,Advanced Surgical Systems).

For the proposed application in treating fibroids, high levels of powerwill be applied for approximately 5-15 minutes. Performance criteria mayinclude power application of 30-50 W/cm² or more for 5 minutes with atleast 40% conversion efficiency, or more.

Referring back to FIG. 6, the therapy delivery system of the presentinvention may include a computer 128 driving a common software interfaceusing LabView and C++ to control RF amplifiers (four or sixteen channel)126 and a 32 channel temperature measurement system. Softwarefunctionality may include user input control of RF power and frequencycontrol for each channel, recording forward/reflected power levels, datalogging amplifier parameters, and alarms at pre-set reflected powerthresholds. Thermometry software may include multi-sensor temperaturesensing, e.g. of sensor array 66, for computing cumulative thermal dose,data logging, and color bars to indicate status of each temperaturepoint (i.e., sublethal, lethal, max threshold). Embedded and C++software may be used for amplifier control and temperature/dosemonitoring and feedback.

FIG. 8 illustrates an exemplary flow diagram for the uterine tumortreatment process of the present invention. First, the applicator (50,80, 100, etc) is positioned to the treatment site at step 160. Directoptical visualization using a laproscope/hysteroscope, and/or viareal-time ultrasound image guidance may be used to direct the applicatortoward the target region.

The treatment parameters (e.g. power, time, frequency) are then input atstep 162 into the computer 128. These parameters are generally afunction of the treatment volume, geometry and location of the lesion,and may be assessed with a pre-operation evaluation.

The power is then activated to the applicator at step 164. Generally,this will take approximately 5-10 minutes, and thermal monitoring may beperformed throughout this step. Preferably, the energy is directedtoward feeding blood vessels and maintained at the target vasculatureuntil temperatures sufficient to collapse and/or destroy the vasculatureare obtained. Thus, it may be sufficient to just heat a portion of thefibroid to obtain the desired therapeutic effect. The applicator mayalso be swept across a region of the fibroid 30 if needed. Temperaturefeedback may be obtained via the deployable thermal sensors 66. Inaddition, the extent of arterial occlusion or other effects of thermaltherapy may be assessed non-invasively during or following heating bydiagnostic techniques such as Doppler ultrasound imaging of the treatedvascular region with contrast media for cases where the vasculature istargeted, fluoroscopy with contrast, MRI T1 contrast enhanced imaging,or contrast enhanced CT imaging. Other monitoring methods includeacoustic harmonic motion imaging, pattern recognition analysis ofbackscatter image data, and acoustic elasticity imaging;

If occlusion is deemed insufficient, the applicator may be turned on toreheat the target tissue. High-temperature thermal ablation withcoagulation of major structural proteins (large thermal doses), or justthermal necrosis alone (low temperatures or thermal exposures) can beused.

At step 166, the power is then turned off, and the device is removedafter target destruction has been completed.

Design criteria for the applicators of the present invention, such asintroducer sheaths, catheter OD limits, stiffness constraints, devicelength, and additional supporting instrumentation, are based on theunique aspects of laparoscopic and hysteroscopic surgeries.

The applicator 50 is configured to treat tissue based on target tissueparameters (e.g. fibroid), and features of the ultrasound transducer(size, frequency, and efficiency), beam distribution, power levels,catheter material, convective cooling, may be varied to account fortissue thermal properties, and dynamic changes in tissue perfusion andultrasound absorption during thermal exposure.

The acoustic attenuation of fibroids is different than typical softtissue, and can range from low for necrotic cores to quite high due tothe high collagen composition and possibly calcification; theattenuation has been reported to range from 0.9-2.2 dB/cm/MHz, andincrease to 1.7-3.3 dB/cm/MHz after HIFU ablation.

Applied power sequences and cooling schemes may also be varied to bestcontrol thermal energy penetration to either maximize the thermal lesion30 size, or to constrain treatment to within a specific radial distancefor safety reasons. This includes applied power sequence (ramp, step,pulsed), applied power requirements, and treatment duration.

Experiment #1

Ultrasound interstitial applicators were evaluated for interstitialhyperthermia for combination with radiation or drug therapy, as well aslocalized thermal ablation. The interstitial ultrasound applicatorsutilized arrays of small tubular ultrasound radiators, designed to beinserted within plastic implant catheters typically used forinterstitial HDR brachytherapy. Water-flow was used during powerapplication to couple the ultrasound and improve thermal penetration.Multi-transducer devices were evaluated with transducer diametersbetween 1.2 mm-3.5 mm and outer catheter diameters between 2.1 mm (14gauge) and 4.0 mm (12 Fr), respectively, with 1.5 mm OD transducers and13 g (2.4 mm OD) catheters the most common configuration. Theapplicators were fabricated with multiple tubular segments, withseparate power control, so that the power deposition or heating patterncould be adjusted in real time along the applicator axis.

The ultrasound energy emanating from each transducer section was highlycollimated within the borders of each segment so that the axial lengthof the therapeutic temperature zone remained well defined by the numberof active elements over a large range of treatment duration and appliedpower levels. FIG. 9 illustrates angular and axial control of powerdeposition (P²) and heating from in vivo measurements of temperature andzones of thermal coagulation. Thus the applicators of the presentinvention are ideally suited to tailor temperature distribution inresponse to anatomy, dynamic changes in perfusion, etc.

Furthermore, the angular or rotational heating pattern, as modified bysectoring the transducer surface, was tested. For example, active zonescan be selected (i.e., 90°, 180°, or 360°) to produce angularlyselective heating patterns. FIG. 10 illustrates the angular distributionof a 200° applicator. Thus, the orientation of the directionalapplicators of the present invention can be used to protect criticalnormal tissue or dynamically rotated and power adjusted to morecarefully tailor the regions of heating.

FIG. 11 illustrates the radial depth of the lesion across the axialposition of the applicator with respect to the three elements. Themulti-element ultrasound applicators were demonstrated to producecontiguous zones of therapeutic temperatures or coagulation betweenapplicators with separation distances of 2-3 cm, while maintainingprotection in non-targeted areas. For the interstitial ultrasounddevices with tubular sources, the radial penetration of energy falls offas 1/r with exponential attenuation and compares favorably to the 1/r2losses of RF needles and 1/rn (n=1−3) losses of microwave antenna. Thespatial control along the length of these ultrasound applicators issuperior to all other interstitial devices, with axial control definedby active elements over a large range of applied power and durations.Operating at high power levels, single applicators can generatesubstantial size thermal lesions ex vivo and in vivo up to 21-25 mmradial distance, within 5-10 min treatment times, while maintainingaxial and angular control of lesion shape. These ultrasound applicatorsprovide the highest level of controllability, and provide more uniformand penetrating heating than all other interstitial heating techniques.

Because of the higher power levels of the applicator 50, the efficiencyand maximum sustainable acoustic output power are important parametersto characterize. The total acoustic power output and conversionefficiency may be measured for varying applicators/transducers usingforce-balance techniques modified for a cylindrical radiation source.The acoustic efficiency as a function of frequency may then bedetermined for each applicator 50 using static force-balancemeasurements. High power output characteristics may then be measured atthe frequency of maximum efficiency.

The quality and pattern of the ultrasound energy output may be assessedwith acoustic beam distributions. Rotational beam plots (output at 360°around the applicator) may also be measured by 3-D scanning of acalibrated hydrophone system (to measure the acoustic pressure-squared).This distribution of energy output is proportional to the powerdeposition within tissue, and is therefore a significantcharacterization to determine thermal therapy potential. Axial, radial,and circumferential fields may be evaluated using iso-intensitycontours. These results may also be correlated to shapes of thermalcoagulation produced during heating trials ex vivo uterine tissue.

Biothermal acoustic models were developed by our group to studyultrasound applicators for hyperthermia and thermal therapy. Thetransient finite-difference model is based upon the Pennes Bioheatequation in cylindrical and Cartesian coordinate system. In order toimprove accuracy, the model incorporates dynamic tissue changes inresponse to accumulation of thermal dose. Specifically, when a t₄₃=300min the blood perfusion reduces to zero and at t₄₃=600 min the acousticattenuation increases 1.5-2 times. This dynamic approach has been usedto model transurethral67 and interstitial ultrasound applicators andshown to be in excellent agreement with experiment. The thermal dosedistribution using the high-temperature therapy t₄₃=240 min is used todefine the boundary of thermal necrosis.

The multi-layered model accepts variable convective heat transfercoefficients, heat capacity, thermal conductivity, density, perfusion,and acoustic attenuation within applicator structures and surroundingtissue. The power deposition is determined by either numerical solutionof the Rayleigh-Sommerfield diffraction integral using the rectangularradiator method, or by empirical determination of geometricdistributions from beam plots.

Simulation of sweeping or rotation of the applicator during thetreatment was also performed. The 2D and 3D models have been applied tosimulate the anticipated heating patterns. FIG. 12 illustrates maximumtemperature contours and lesion shapes for r-z simulations of aninterstitial ultrasound applicator heating in vivo thigh muscle for 3min with (a) one, (b) two, (c) three active transducers. The solid blackcontour lines represent simulated lesion shapes, and the dashed contourlines represent experimental in vivo measurements of lesions generatedafter 3 min of heating with 30 W/cm2 applied electrical power perelement in pig thigh muscle. FIG. 13 illustrates 3D calculations for atwo element interstitial applicator.

The ultrasound applicators of the present invention are amenable toaccurate MR image-based treatment planning and thermal monitoringsimilar to MR-guided focused ultrasound procedures. As shown in FIG. 14,MR thermal imaging can be used to map the temperature elevations andthermal dose (outer contour line) during the application ofpower/treatment, as demonstrated for high-temperature application invivo (3 slices, 6 mm apart). FIG. 14 demonstrates thermal ablativetemperatures in perfused tissue from cooled 3.5 mm OD transducer array.

To test the ultrasound applicator devices, heating trials were conductedin ex vivo uterine fibroid tissue, obtained directly after surgicalremoval (hysterectomy or myomectomy). Because fibroids do not naturallydevelop in the uterine tissue of other mammals, there is no satisfactoryanimal model to test the applicator performance in a more realistic invivo environment. Although there is no blood flow in the ex vivo and invitro tissue samples, imaging studies of uterine fibroids have shownthat perfusion in the fibroid tissue is typically low, especially in thecenter of the tumor where the vasculature has been replaced by anecrotic core. Such heating trials provide a controlled experimentalenvironment where detailed and repeatable tests can be conducted fordirect comparison of applicator performance (which is considerably moredifficult to achieve in vivo). Thus, the use of ex vivo uterine tissuesamples provides the best approximation to the clinical case.

The heating trials were performed with a 2.4 mm OD ultrasound applicatorinserted into a pathologic fibroid tissue sample, which was placed in atemperature-controlled waterbath (37° C.). Arrays of miniaturethermocouple probes were placed in the tissue, using a template toensure proper alignment. The probes were multiple junctionconstantan-manganin sensors, encased in thin-walled polyimide tubing,and inserted within 22-g thin walled needles for minimal thermalconduction and ultrasound artifact. The thermocouples were used tomeasure radial and axial temperature distributions (and resultingthermal dose) in the tissue, and were recorded using a 32-channelthermometry system with fast data acquisition interfaced to a computer.Placement verification was performed using a portable fluoroscopic unit.Multiple heating trials will be performed with varied applicatorparameters of applied power levels, heating times, coolant flows, andactive transducer elements for each applicator under test. Followingsonication, the tissue was sliced along the transverse and longitudinalaxes to measure the boundary and volume of visible thermal coagulation.

The measured radial temperature distributions after 10 minutes ofheating using a three element hyperthermia applicator are shown in FIG.15. As shown in FIG. 15, large volumes of tissue (2.5-3.0 cm radius×3.0cm length, or ˜85 cm³) were thermally destroyed (e.g. temperature>50°C., lethal thermal dose>240 min) using this approach.

Experiment #2

A family of interstitial ultrasound applicators was fabricated using 2-4cylindrical piezo-ceramic crystal transducers (PZT-4) with outerdiameters (OD) of 1.5 or 2.5 mm and lengths of 10-15 mm. Theconfigurations tested were 1.5 mm OD×10 mm long transducers in lineararrays of two, three and four adjacent transducers, an array of three2.5 mm OD×15 mm long adjacent transducers, and an array of one 2.5 mmOD×15 mm long transducer adjacent to two 2.5 mm OD×10 mm transducers.

The operating frequencies of the transducers ranged from 6.5 to 8 MHz.For some of the applicators, the transducers were sectored to produce a180° actively acoustic sector for directional power deposition. Thetransducers were mounted on support structures, and a bio-inert plasticlayer was applied for electrical and biological insulation. The 1.5 mmOD applicators were inserted into 13 gage brachytherapy catheters (2.4mm OD), and the 2.5 mm OD applicators into custom PET catheters (3.7 mmOD). Degassed water was circulated through the applicators to cool thetransducers during operation, to couple the ultrasound energy to thetissue, and to potentially control temperature at the tissue-catheterinterface allowing for greater radial penetration of thermal energy.

Measurements of electrical impedance (Z) and acoustic efficiency (η)were obtained for each transducer. Z was measured as a function offrequency (5≦f≦10 MHz) using a network analyzer (Hewlett Packard Model#3577A). η was measured as a function of frequency using the forcebalance technique for cylindrical radiators, and is determined as theratio of acoustic output power to the applied electrical power.Measurements for the applicators were made with no catheters in placethen repeated with the applicators inserted in catheters with a waterflow rate of 40 ml/min⁻¹. These were used to determine the optimaldriving frequencies, and to determine how much acoustic energy is beingdelivered to the tissue.

The acoustic efficiency data for each transducer type is summarized inTable 1. As expected, there was a 30-40% decrease in η when theapplicators were placed in the catheters due to loss of acoustic energyin the catheter wall.

FIG. 16 illustrates the test setup for human uterine fibroids obtainedimmediately after removal during routine surgical open myomectomies. Thefibroids 202 were instrumented with an interstitial ultrasoundapplicator 210 and six 20 gage thin-walled spinal needles 212 placed atradial distances of 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 cm from theapplicator 210, and scattered in angle for thermometry. A 6 cm×8 cm×1 cmplexiglass template 214 was used to ensure alignment of the applicator210 and spinal needles 212. The instrumented fibroid 202 was then placedin a 37° C. circulating waterbath 204, and allowed to reach equilibrium.Custom, multi-junction contantan-manganin thermocouple probes consistingof linear arrays of either four 50 μm junctions spaced at 2.5 mm, orseven 50 μm junctions spaced at 5 mm, were inserted into the spinalneedles. A 4 channel amplifier with built-in function generator andpower monitoring (Advanced Surgical Systems, Inc.) was used to drive thetransducers.

Several heating trials were performed to investigate the effects ofapplicator 210 size (2.4 mm OD vs. 3.7 mm OD), directional heatingcapability (180° vs. 360° heating patterns), and number and size ofactive elements 64 (2-4 transducers) on thermal lesion formation (seeTable 2). Temperatures were recorded every 3 s at each sensor location(up to 27 data points) using a computer controlled data acquisitionsystem with in-line RF filtering.

FIGS. 17-19 illustrate the results of the heating trial in a humanuterine fibroid using a 4-element applicator with 360 degree heatingpattern inserted in a 13 g catheter with 60 ml/min flow rate (f=8.2-8.5MHz, 15 W to three elements for 8 minutes). FIG. 17 shows the measuredtransient temperature curves (each curve represents the average of 4sensors at each radial depth of 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 cm).FIG. 18 is a graph of the radial temperature distribution after heatingfor 2, 4, 6 and 8 minutes, and average accumulated thermal dose at eachradial depth after heating for 8 minutes. FIG. 19 is the temperaturedistribution measured at 1 cm radial distance along the length of theapplicator with 3 active elements at 2 minute time intervals.

The accumulated iso-effect thermal dose was calculated from thetemperature-time history at each point according to:

$t_{43} = {\sum\limits_{t = 0}^{t - {final}}\; {R^{T - 43}\Delta \; t}}$

where t₄₃ is the equivalent time at 43° C., T is the average temperatureduring time Δt, and R is a constant based on the activation energy andabsolute temperature from the Arrhenius relationship (R=2 for T≧43° C.,R=4 for T<43° C.).

After heating, the tissue was sliced into sections approximately 5-10 mmthick. Since the thermal lesions were not clearly visible, the tissuesections were placed into a 2% solution of 2,3,5-triphenyltetrazoliumchloride (TTC) for approximately 20 minutes. TTC is a tissue viabilitystain that allows for visualization of acute, lethal tissue damage at amacroscopic level. Measurements of visible thermal lesions were thenobtained, and the tissue sections then placed in a 10% buffered Formalinsolution for fixation, and later sectioning. Standard hematoxylin andeosin (H&E) stained sections were obtained for histological evaluation.

FIG. 20 illustrates a sagittal slice through thermal lesion 30,visualized after 20 minutes in a 2% TTC solution (measureddimensions=3.5 cm diameter×3.9 cm long).

FIGS. 21 and 22 illustrate transverse slices through thermal lesions (asvisualized using TTC stain) generated in human uterine fibroids using a3-element applicator with a 180 degree directional heating pattern,inserted in a 3.7 mm OD catheter with 60 ml/min flow rate (f=6.6-7.6MHz). FIG. 21 illustrates a directional lesion produced by 15 W to twoelements for 7 minutes (fibroid was at thermal equilibrium in a 28° C.waterbath; lesion radius=1.2 cm). Maximum temperatures measured atradial distances of 0.5, 1.0, and 1.5 cm from the applicator are shownwith corresponding accumulated thermal dose.

FIG. 22 is a directional lesion produced by 15 W to three elements for15 minutes (lesion radius=1.7 cm). Maximum temperatures measured atradial distances of 0.5, 1.0, 1.5, 2.0, and 2.5 cm from the applicatorare shown with corresponding accumulated thermal dose. Position of theapplicator and direction of energy delivery are shown by the whitecircle with arrow for both FIGS. 21 and 22.

FIGS. 23 and 24 illustrate H&E stained sections of human uterine fibroidtissue (at 400× magnification). FIG. 23 illustrates untreated tissueshowing lighter, heterogeneous and slightly granular chromatin, andvisible nuclear features. FIG. 24 shows treated tissue indicatinghyperchromatic nuclei with no visible features and homogenously darkchromatin. Cytoplasm also appears slightly darker than the untreatedtissue.

FIGS. 25-28 illustrate additional tests performed with varyingapplicators and distribution patterns. FIG. 25 illustrates a three-10 mmtransducer applicator and resulting tissue lesion. The size of thelesion in FIG. 25 is directly correlated to the applicator transducergeometry, particularly when compared to the lesion achieved by thefour-10 mm transducer applicator shown in FIG. 26. FIG. 27 illustrates alesion created by a two-10 mm transducer applicator with 180°directional distribution. FIG. 28 further illustrates a 180° directionaldistribution applicator applied at an insertion point.

Results from this study demonstrated that thermal lesions greater than1.5-1.7 cm radial depth (3-3.5 cm diameter) and up to 5 cm in length (asevidenced by staining with TTC) could be produced in human fibroidtissue in less than 10 min with 15 W of applied electrical power.Further, therapeutic temperatures greater than 50° C., and potentiallylethal thermal doses extended beyond 2.0 cm radially from the applicator(>4 cm diameter). Histological examination of heated tissue revealedhyperchromatic nuclei with homogeneously dark chromatin, and no visiblenuclear features, as compared to untreated tissue.

In conclusion, high-Intensity interstitial ultrasound thermal treatmentof uterine fibroids can potentially be used to access treatment of morefibroids and patients than possible with existing technologies, andprovide a safer easier approach with lower morbidity, shorter treatmentduration, and lower procedure costs.

Interstitial ultrasound provides exceptional control over the heatinglength and radial depth, and ability to have selective heating patternsprovides an innovative interstitial thermal ablation technology that canbe applied to treat fibroids more consistently, more thoroughly, andfaster following procedures that can be routinely applied bygynecological surgeons. This superior spatial control can be used tosafely target a larger number of fibroids than can be treated withexisting ablative technology. Interstitial ultrasound technologyprovides the ability to treat a targeted fibroid region whilesimultaneously protecting other non-targeted healthy tissue.

It is believed that thermal myolysis may preserve the integrity of theuterine wall with uncomplicated full-term pregnancies and uneventfulvaginal deliveries post procedure are reported. This indicates thatminimally-invasive thermal ablation of uterine fibroids may become atreatment of choice for women still considering having children,significantly increasing the number of patients that could benefit fromprecise and selective high-intensity interstitial ultrasound treatment.

Only certain fibroids can be removed by laparoscopy. If the fibroids arelarge, numerous, or deeply embedded in the uterus, then an abdominalmyomectomy or hysterectomy may be necessary. With laparoscopicinterstitial thermal ablation, these fibroids that are too large forsurgical removal can be treated in situ in a minimally-invasive fashion.A single insertion of an interstitial ultrasound applicator can treatlarger fibroids than possible with multiple insertions of existingtechnology.

In addition, it is proposed that thermal ablation and resultant thermalfixation of tissue produces a faster less painful recovery compared tothe painful ischemic necrosis of fibroids and uterine tissue encounteredin patients post-UAE procedures.

Although the description above contains many details, these should notbe construed as limiting the scope of the invention but as merelyproviding illustrations of some of the presently preferred embodimentsof this invention. Therefore, it will be appreciated that the scope ofthe present invention fully encompasses other embodiments which maybecome obvious to those skilled in the art, and that the scope of thepresent invention is accordingly to be limited by nothing other than theappended claims, in which reference to an element in the singular is notintended to mean “one and only one” unless explicitly so stated, butrather “one or more.” All structural, chemical, and functionalequivalents to the elements of the above-described preferred embodimentthat are known to those of ordinary skill in the art are expresslyincorporated herein by reference and are intended to be encompassed bythe present claims. Moreover, it is not necessary for a device or methodto address each and every problem sought to be solved by the presentinvention, for it to be encompassed by the present claims. Furthermore,no element, component, or method step in the present disclosure isintended to be dedicated to the public regardless of whether theelement, component, or method step is explicitly recited in the claims.No claim element herein is to be construed under the provisions of 35U.S.C. 112 unless the element is expressly recited using the phrase“means for” or “step for”.

TABLE 1 Acoustic efficiency (η) data for the three transducer geometriesused in this study. Measurements were made without catheters, thenrepeated with catheters (flow rate = 40 ml/min). Transducer Descriptionf (MHz) η (no catheter) η (in catheter) Catheter 1.5 mm OD × 7.2 52% 32%2.4 mm OD 10 mm long 2.5 mm OD × 6.6 59% 35% 3.7 mm OD 10 mm long 2.5 mmOD × 7.6 62% 36% 3.7 mm OD 15 mm long

TABLE 2 Thermal lesion dimensions measured using different applicatorconfigurations # Elements Applicator/Catheter Power (W) Time (min)Lesion Dimensions (cm) 4 1.5 mm OD/2.4 mm OD 15 per chan. 8 3.5 dia. ×5.0 long^(a) 3 1.5 mm OD/2.4 mm OD 15 per chan. 8 3.5 dia. × 3.9long^(a) 2 1.5 mm OD/2.4 mm OD 12 per chan. 8 1.5 rad. × 2.5 long^(b) 32.5 mm OD/3.7 mm OD 15 per chan. 15 1.7 rad.^(b) 2 2.5 mm OD/3.7 mm OD15 per chan. 7 1.2 rad.^(b,c) Notes: ^(a)360 degree heating pattern;^(b)180 degree directional heating pattern; ^(c)Tissue was at thermalequilibrium in a 28° C. waterbath rather than a 37° C. waterbathresulting in smaller lesion size

What is claimed is:
 1. An apparatus for treating uterine fibroids, theapparatus comprising: (a) a catheter having a distal end and a proximalend; and (b) an ultrasound applicator disposed at the distal end of saidcatheter, the ultrasound applicator comprising: one or more transducersdisposed longitudinally along a central axis of the catheter; the one ormore transducers being coupled to a power source external to saidcatheter; (c) wherein the ultrasound applicator is configured to bepositioned to a treatment location at or near a fibroid tissue mass anddeliver high-intensity ultrasound energy sufficient to therapeuticallyheat said fibroid tissue mass.